Single nucleotide polymorphism rs6716901 in SLC25A12 gene is associated with Asperger syndrome

Jaroslava Durdiaková,Bhismadev Chakrabarti,Simon Baron-Cohen,Varun Warrier

doi:10.1186/2040-2392-5-25

Abstract

BackgroundAutism Spectrum Conditions (ASC) are a group of developmental conditions which affect communication, social interactions and behaviour. Mitochondrial oxidative dysfunction has been suggested as a mechanism of autism based on the results of multiple genetic association and expression studies. SLC25A12 is a gene encoding a calcium-binding carrier protein that localizes to the mitochondria and is involved in the exchange of aspartate for glutamate in the inner membrane of the mitochondria regulating the cytosolic redox state. rs2056202 SNP in this gene has previously been associated with ASC. SNPs rs6716901 and rs3765166 analysed in this study have not been previously explored in association with AS.MethodsWe genotyped three SNPs (rs2056202, rs3765166, and rs6716901) in SLC25A12 in n?=?117 individuals with Asperger syndrome (AS) and n?=?426 controls, all of Caucasian ancestry.Resultsrs6716901 showed significant association with AS (P?=?0.008) after correcting for multiple testing. We did not replicate the previously identified association between rs2056202 and AS in our sample. Similarly, rs3765166 (P?=?0.11) showed no significant association with AS.ConclusionThe present study, in combination with previous studies, provides evidence for SLC25A12 as involved in the etiology of AS. Further cellular and molecular studies are required to elucidate the role of this gene in ASC.

Highlights

Autism Spectrum Conditions (ASC) are a group of developmental conditions which affect communication, social interactions and behaviour
Participants in the control group were asked to complete an online version of the Autism Spectrum Quotient (AQ) test [21], which is a measure of autistic traits
We identified an association between rs6716901 and Asperger syndrome (AS) in our sample. rs2056202 has been reported to be nominally associated with ASC in Irish and Finnish samples [14,15]

Summary

Introduction

Autism Spectrum Conditions (ASC) are a group of developmental conditions which affect communication, social interactions and behaviour. SLC25A12 is a gene encoding a calcium-binding carrier protein that localizes to the mitochondria and is involved in the exchange of aspartate for glutamate in the inner membrane of the mitochondria regulating the cytosolic redox state. Autism Spectrum Conditions (ASC) are a group of neurodevelopmental conditions characterised by difficulties in social interaction and communication, alongside unusually narrow interests and repetitive, stereotyped behaviour [1]. SLC25A12 is expressed primarily as 2.9and 3.2-kb mRNA species, predominantly in skeletal muscle, heart, and brain [6,9] It encodes a calciumbinding carrier protein, the mitochondrial aspartateglutamate carrier isoform 1, which localizes to the mitochondria and is involved in the exchange of the aspartate for glutamate in the inner mitochondrial membrane regulating the cytosolic redox state. It enables mitochondrial oxidation of cytosolic nicotinamide adenine dinucleotide (NADH), thought to be important in providing energy for neurons in the central nervous system (CNS) [10,11]

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